The principal objectives of this proposal are: 1) to determine the role of K ion, osmolarity, and inorganic phosphate as mediators of active hyperemia in soleus and gracilis muscles of cats; 2) to determine the relationship between blood flow and metabolism in soleus and gracilis muscles of cats; 3) to determine the role of adenosine as a mediator of local control of blood flow in skeletal muscles of dog during active hyperemia, reactive hyperemia, and autoregulation of blood flow; and 4) to determine whether vasodilation in bioassay muscle perfused with blood from contracting donor muscle results from limitation of oxygen consumption in bioassay muscle. We propose to study the metabolically-linked local regulation of blood flow in three skeletal muscle preparations that are relatively homogeneous with respect to fiber type and have metabolic patterns ranging from low oxidative and high glycolytic capacities to high oxidative capacity. Soleus muscle in cats is composed of slow twitch, oxidative fiber types. Gracilis muscle in cats is composed of fast twitch, low oxidative fiber types. These are the two fiber types of which human skeletal muscles are composed. Skeletal muscles of dogs are composed of fast twitch, high oxidative fiber types. The circulations of the muscle preparations will be isolated so that blood flow and the uptake or release of various substances for a single muscle can be measured. The proposed studies will enhance our understanding of the metabolic response to changes in muscle activity and how that metabolic response is translated into changes in blood flow. These studies will also enable us to determine the conditions under which the factor limiting muscle performance is the oxidative capacity of the muscle and under which it is oxygen supply, limited by blood flow. Once we gain a better understanding of the relationship between metabolism and blood flow in normal animals, we can begin to determine how various disease states alter the relationship and how we might intervene to correct this alteration.